ZY Biosciences Advances China's First Live Biotherapeutic Drug SK08 into Phase II Clinical Trials, Building an Integrated 'Bug-to-Drug' Development Platform

From scientific research to industrialization, Dr. Liu Yangyang has consistently focused on the gut microecological system. Microecological research is a scientific discipline dedicated to studying the structure and function of living microbial communities and their interactions with the host. Since these living microbes are inevitably derived from fecal matter, Dr. Liu humorously describes his past research experience as “abandoning clinical medicine to scoop feces.”

Dr. Liu Yangyang, Co-founder of ZYBio

Dr. Liu Yangyang holds a Ph.D. from Southern Medical University and has dedicated many years to the research and development of therapeutic approaches for digestive diseases. He was a core member of the Guangzhou Innovative Leading Team in 2017, recognized as a Pearl River Science and Technology New Star in Guangzhou in 2018, and named one of Guangdong Province’s Top 100 Innovative Doctors and Postdoctoral Fellows in 2019. Additionally, he served as a key member of the National 863 Program. Dr. Liu has presided over or participated in ten national, provincial, and municipal scientific and technological projects, published 14 SCI-indexed papers, and filed more than 30 invention patents, with seven already granted.

It was also this valuable “dirty work” experience at Southern University of Science and Technology that enabled Dr. Liu Yangyang’s research group to fortuitously discover a special strain of Bacteroides fragilis during their scientific research, which holds potential for curing digestive diseases. This special strain, named SK08, later became the origin of ZYBio.

In 2013, Guangzhou Zhiyi Biological Technology Co., Ltd. (hereinafter referred to as "ZYBio") was established and registered. SK08 transitioned from scientific research to industrialization research, and the company simultaneously initiated safety evaluation and preclinical studies for SK08. ZYBio also became one of the earliest enterprises in China to conduct microbiome research.

However, when ZYBio was first established, the domestic environment for live biotherapeutic product (LBP) development was unfavorable. Dr. Liu Yangyang told VCBeat that in the early stages, the company attempted to engage contract research organizations (CROs) capable of providing LBP-related services, but such capabilities were severely lacking across the entire CRO market. Consequently, ZYBio had no choice but to forge its own path through trial and error, ultimately establishing a GMP-compliant manufacturing facility with a complete production line.

ZYBio's SK08 Live Bacterial Powder

In 2017, ZYBio completed the construction of its R&D center and manufacturing facilities in Guangzhou Science City, received support from the Guangdong Provincial Special Fund for Technology Achievement Transformation in 2017, published progress on its second-generation probiotic R&D in a Nature subsidiary journal, and subsequently released SK08-related research findings internationally; in 2018, SK08 obtained an Investigational New Drug (IND) approval; in 2019, SK08 initiated clinical trials, becoming the only live biotherapeutic product approved by the National Medical Products Administration (NMPA) currently available for clinical use aside from gynecological products (developed using common strains), and representing the first orally administered formulation globally to be developed as a Live Biotherapeutic Product (LBP) using the novel strain Bacteroides fragilis.

Currently, there are very few live biotherapeutic products (LBPs) approved internationally; however, there are approximately 40 LBP candidates in clinical development worldwide, including fecal microbiota, microbial consortia, multi-strain formulations, single-strain agents, and engineered bacteria. The number of preclinical LBP candidates is even larger, with indications spanning autoimmune diseases, oncology, and infectious diseases. In the early discovery stage, the scope of indication exploration for LBPs is broader, encompassing metabolic disorders, combination therapies for cancer treatment, and the use of engineered bacteria to deliver antibodies for tumor therapy.

SK08 is a strain of *Bacteroides fragilis*, with its primary indications being irritable bowel syndrome (IBS) and ulcerative colitis (UC). Currently, ZYBio has advanced the SK08 clinical pipeline to Phase II clinical trials, and the company is actively conducting these studies.

In contrast, the most advanced live biotherapeutic products abroad have only reached Phase III clinical trials. ZYBio’s R&D pace remains largely on par with its international peers, positioning it in the first tier of live biotherapeutic product development both domestically and globally.

ZYBio is dedicated to the research and development of NGPs (Next-Generation Probiotics) and LBPs (Live Biotherapeutic Products), serving as a leading domestic platform for the industrial translation of innovative microbiome achievements. The company’s core team comprises clinical experts in gastroenterology, specialists in fundamental microbiological research, drug development experts, and seasoned entrepreneurs, supported by a frontline research team primarily composed of individuals with doctoral and master’s degrees.

Leveraging its prior technological and industrialization platform advantages, ZYBio is progressively establishing a research and product development platform of international caliber focused on the relationship between human pathogenic commensal bacterial spectra and diseases, screening of novel functional strains, and target identification. Currently, the company has established a comprehensive technical system in the areas of microbial and pathogenic bacterial spectra, isolation of novel functional strains and target identification, as well as the development of new live biotherapeutic products and active ingredient-based drugs. Meanwhile, it possesses a complete industrialization platform covering the entire process from preclinical studies to New Drug Application (NDA).

ZYBio Laboratory

Liu Yangyang told VCBeat that, after several years of development and in the process of advancing SK08 into clinical trials, ZYBio has gradually established a know-how system for live biotherapeutic products. This system covers dosage form development and stability studies, development of related analytical methods, research on fermentation and formulation manufacturing processes, isolation and development of bacterial active ingredients, risk factor assessment and control, and the establishment of a GMP system for live biotherapeutic products.

Leveraging this platform, ZYBio has been able to rapidly evaluate the druggability of candidate strains, conduct preclinical studies, and advance them into clinical trials. Currently, ZYBio has also established a clinical pipeline for other novel live biotherapeutic products, as well as biologics and chemical drugs with bacterial activity, with indications expanding into areas such as oncology; these candidates are currently in the preclinical research stage. With its mature technology platform, the company plans to submit 1–2 Investigational New Drug (IND) applications annually, thereby accelerating entry into clinical trials.

Meanwhile, ZYBio maintains a backup strain library comprising tens of thousands of bacterial strains, enabling the annual identification of 1–2 candidate live biotherapeutic products with drug-like potential, thereby enriching its clinical pipeline. Liu Yangyang also acknowledged that studying the druggability of live biotherapeutics is the most critical aspect, as it determines whether a specific strain is suitable for disease treatment. Conversely, live biotherapeutics offer a higher safety profile compared to chemical drugs. Furthermore, unlike the “point-to-point” mechanism of chemical drugs, live biotherapeutics exert more complex and comprehensive effects, providing therapeutic advantages in treating highly complex diseases.

Currently, ZYBio has established a 5,000-square-meter R&D center and manufacturing facility, featuring domestically leading GMP workshops for fermentation (50L–500L–5000L), active ingredient separation and purification, and formulation. This represents the first complete GMP production line in South China, spanning from fermentation to final drug product formulation. The company has initiated industrialization collaborations with various universities and enterprises, covering the screening, functional evaluation, and industrial development of live biotherapeutic products.

It is reported that ZYBio completed its RMB 110 million Series B financing round at the end of 2020. The company plans to initiate a new round of financing after obtaining the Investigational New Drug (IND) approval for its live biotherapeutic product derived from novel bacterial strains.